Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA270765 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Breaking the first lineage barrier: Direct induction of trophoblast stem cells from murine fibroblasts
| PRJNA270252 | ENA
Project description:Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here, we define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Our integrated analysis reveals differences in the relative abundance and activities of distinct chromatin modules. We identify a strong enrichment of Polycomb Repressive Complex 2 (PRC2)-associated H3K27me3 in naive pluripotent stem cell chromatin, and H3K27me3 enrichment at promoters of lineage-determining genes, including trophoblast regulators. PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, while inhibition of PRC2 promotes trophoblast fate induction and cavity formation in human blastoids. Together, our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates.
2022-05-09 | PXD032792 | Pride
Project description:Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here, we apply multi-omics to comprehensively define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Integrating the chromatin-bound proteome and histone modification data sets reveals differences in the relative abundance and activities of distinct chromatin modules, identifying a strong enrichment of Polycomb Repressive Complex 2 (PRC2)-associated H3K27me3 in naive pluripotent stem cell chromatin. Single-cell approaches and human blastoid models reveal that PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, and inhibiting PRC2 promotes trophoblast fate induction and cavity formation. Our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates.
2022-05-06 | PXD028111 | Pride
Project description:Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here, we apply multi-omics to comprehensively define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Integrating the chromatin-bound proteome and histone modification data sets reveals differences in the relative abundance and activities of distinct chromatin modules, identifying a strong enrichment of Polycomb Repressive Complex 2 (PRC2)-associated H3K27me3 in naive pluripotent stem cell chromatin. Single-cell approaches and human blastoid models reveal that PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, and inhibiting PRC2 promotes trophoblast fate induction and cavity formation. Our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates. Data originating from the LC-MS/MS analysis of the histone PTMs can be consulted via this project.
2022-05-06 | PXD028162 | Pride
Project description:Trophoblast stem cells represent the stem cell population of the extra-embryonic lineage and arise as a result of the first cell fate decision. From blastocyst stage onwards, a distinct epigenetic lineage barrier strictly separates mouse embryonic and extra-embryonic lineages. Recently, it has been shown that this epigenetic barrier cannot be fully overcome as the expression of TS-determining factors in embryonic stem cells lead to incomplete transdifferentiation. Here, we demonstrate that transient expression of Tfap2c, Gata3, Eomes and Ets2 in fibroblasts suffices to generate cells which are almost identical to trophoblast stem cells based on morphology, expression and methylation pattern. Further, these induced trophoblast stem cells display transgene independent self-renewal, differentiate along the extra-embryonic lineage and chimerize the placenta upon blastocyst injection. Our findings provide insights into the transcription factor networks governing trophoblast stem cell identity and offer a new tool for studying the hierarchy of those factors.
2015-10-01 | GSE64145 | GEO
Project description:Trophoblast stem cells represent the stem cell population of the extraembryonic lineage and arise as result of the first cell fate decision. From the blastocyst stage onwards, the extraembryonic lineage is strictly separated from the embryonic lineage by a distinct epigenetic lineage barrier. Recently, it has been shown, that this epigenetic barrier cannot be fully overcome as the expression of TS-determining factors in embryonic stem cells lead to incomplete trans-differentiation. Here we demonstrate that transient expression of Tfap2c, Gata3, Eomes and Ets2 in fibroblasts suffices to generate cells, which are almost equivalent to trophoblast stem cells based on morphology, expression and methylation patterns. Further, these induced trophoblast stem cells display self-renewal without exogenous factor expression, differentiate along the extraembryonic lineage and chimerize the placenta upon blastocyst injection. Our findings provide insights into transcription factor networks governing TSC identity and offer a new tool for studying the hierarchy of those factors.
2015-10-01 | GSE64339 | GEO
Project description:Comprehensive quantitative proteomic study of human pre-implantation embryo stages reveal dynamic proteome landscape from M2, 8-cell and blastocyst stage, and during trophoblast stem cell (TS) differentiation. Identified key factors in early human embryos and lineage-specific trophoblast proteome profiles, correlated with transcriptomic analyses. This direct proteomic analysis provides a comprehensive analysis of the dynamic protein expression in human embryos during pre-implantation development and a powerful resource to enable further mechanistic studies on human trophoblast development and function.
2023-07-05 | MSV000092349 | MassIVE
Project description:Recent advances have suggested that direct induction of neural stem cells could provide an alternative to derivation from somatic tissues or pluripotent cells. Here we show direct derivation of stably expandable NS cells from mouse fibroblasts through a curtailed version of reprogramming to pluripotency. By constitutively inducing Sox2, Klf4, and c-Myc while strictly limiting Oct4 activity to the initial phase of reprogramming, we generated neurosphere-like colonies that could be expanded for more than 50 passages and do not depend on sustained expression of the reprogramming factors. These induced NS (iNS) cells uniformly display morphological and molecular features of NS cells such as the expression of Nestin, Pax6, and Olig2 and have a similar genome-wide transcriptional profile to brain-derived NSCs. iNS cells can differentiate into neurons, astrocytes and oligodendrocytes in vitro and in vivo. Our results demonstrate that functional neural stem cells can be generated from somatic cells by factor-driven induction. mRNA extracted from Murine Embryonic Fibroblasts (MEF), murine Embryonic Stem Cell (ES), murine Neuronal Stem Cell (NS) and three murine induces Neuronal Stem Cell clones 2, 3 and 5 (iNS2, iNS3, iNS5) has been hybridized on Illumina MouseWG6 V2 arrays for genome wide expression analysis. Samples were run at least as triple, MEF, iNS3, iNS5 as quadruple technical replicates. Differential gene expression analysis has been performed on the grouped expression data with the Murine Embryonic Fibroblasts group as the reference.
2012-04-11 | E-GEOD-36484 | biostudies-arrayexpress
Project description:Direct Conversion of Trophoblast Stem Cells into Pluripotent Stem Cells by Oct4
| PRJNA134681 | ENA
Project description:GATA transcription factors, particularly GATA2 and GATA3 are selectively expressed in the extraembryonic trophoblast lineage and regulates gene expression to promote trophoblast self-renewal during mammalian development. However, we have a poor understanding about the contribution of these GATA factors, in the process of syncytiotrophoblast (SynT) development. Thus, the goal of this study is to define the importance of GATA2 and GATA3 in orchestrating a global gene expression program that poises and commits mammalian trophoblast stem cells to the SynT lineage. Using the cut and run technique for GATA2 and GATA3 antibodies in the human trophoblast stem cells we are aiming to identify the direct targets of the GATA transcription factors that are essential for determining the SynT lineage. Three individual experiments were performed.
2024-01-26 | GSE214486 | GEO